Document Detail


Tissue distribution and pharmacokinetics of stable polyacrylamide nanoparticles following intravenous injection in the rat.
MedLine Citation:
PMID:  21134391     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A variety of polymer nanoparticles (NP) are under development for imaging and therapeutic use. However, little is known about their behavior. This study examined pharmacokinetics, distribution and elimination of stable polyacrylamide (PAA) nanoparticles (~31 nm average diameter). PAA NPs and polyethylene glycol-coated PAA NPs were injected into the tail veins of healthy male rats. Blood, tissues and excreta were collected at times ranging from 5 min to 120 h and their radioactive content was quantified. A mathematical model was then applied to analyze the distribution dynamics of both NPs. Elimination from the blood could be accounted for by a quick but finite relocation to the major organs (about 20%, 0.6 to 1.3h half-lives), and a slower distribution to the carcass (about 70%, 35 to 43 h half-lives). Excreted urinary levels correlated with blood concentrations. Combined cumulative urinary and fecal output accounted for less than 6% of the dose at 120 h. Compared to five other polymeric nanoparticles, the studied particles are at the highest half-lives and Area Under the Curve (4000 to 5000%-h). These two parameters decrease by three orders of magnitude when nanoparticle size increases from the 30 nm range up to 250 nm. For similar sizes, pegylated nanoparticles are more persistent in the blood than non-pegylated ones, but this difference is much smaller in the 30 nm and relatively high dose range than above 100 nm. Persistence of PAA NPs is not associated with acute toxicity signs as measured by typical serum markers of inflammation and cellular damage.
Authors:
Yvan Wenger; Randal J Schneider; G Ramachandra Reddy; Raoul Kopelman; Olivier Jolliet; Martin A Philbert
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2010-12-04
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  251     ISSN:  1096-0333     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-03-01     Completed Date:  2011-04-13     Revised Date:  2012-03-19    
Medline Journal Info:
Nlm Unique ID:  0416575     Medline TA:  Toxicol Appl Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  181-90     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Risk Science Center, Department of Environmental Health Sciences, 109 S Observatory, University of Michigan School of Public Health, Ann Arbor, MI 48109-2029, USA. yvan@umich.edu
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MeSH Terms
Descriptor/Qualifier:
Acrylic Resins / administration & dosage,  pharmacokinetics*,  toxicity
Animals
Area Under Curve
Drug Carriers / administration & dosage,  pharmacokinetics*,  toxicity
Half-Life
Injections, Intravenous
Male
Models, Theoretical
Nanoparticles*
Particle Size
Polyethylene Glycols / administration & dosage,  pharmacokinetics*,  toxicity
Rats
Tissue Distribution
Toxicity Tests, Acute
Grant Support
ID/Acronym/Agency:
N01-CO-37123/CO/NCI NIH HHS; R01 EB007997/EB/NIBIB NIH HHS; R01 ES008846-11/ES/NIEHS NIH HHS; R01 ES08846/ES/NIEHS NIH HHS; U01 ES020128-01/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Acrylic Resins; 0/Drug Carriers; 0/Polyethylene Glycols; 9003-05-8/polyacrylamide

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